Reperfusion of ischemic tissue often leads to an acute inflammatory response, which acts directly to aggravate the injury in the reperfused zone, characterized by adhesion and subsequent infiltration of inflammatory cells that injure the tissue through the generation of
oxygen-derived
free radicals and release of various inflammatory mediators. The rapid
edema formation associated with
reperfusion injury is induced by increased microvascular permeability to
plasma proteins and/or increased net filtration pressure across the microvascular wall, and the latter is at least in part induced by lowering of the interstitial fluid pressure (P(if)). We investigated the anti-inflammatory effect of
alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on
edema formation, microvascular
protein leakage, and P(if) in rat hind limb after
ischemia-reperfusion (I/R) injury. There was significant increase of both
albumin extravasation from 0.02 +/- 0.02 to 0.41 +/- 0.21 mL g dry weight-1 (P < 0.05) and total tissue water from 1.08 +/- 0.07 to 1.65 +/- 0.55 mL g dry weight(-1) (P < 0.05) in the skin of paws undergoing I/R injury. P(if) was significantly lowered from -0.51 +/- 0.34 to -5.00 +/- 1.53 mmHg (P < 0.05) concomitant with substantial
edema formation. The
edema formation, and lowering of P(if) during I/R injury was significantly lowered and nearly totally abolished in the animals treated with
alpha-trinositol 30 min before reperfusion. We conclude that
alpha-trinositol limits the increased vascular permeability and
edema formation by preventing the decrease in P(if) as well as acting protective on the microvascular wall.